1. Field of the Invention
This invention relates to an ophthalmic surgery auxiliary agent which contains of collagen. In more detail, the invention relates to an ophthalmic surgery auxiliary agent containing collagen whose viscosity drops and becomes easier to remove when the operation is over.
2. Description of the Prior Art
During ophthalmic surgery such as a removing of crystalline lens, a transplant operation of artificial crystalline lens, a trimming at the transplantation of cornea or a transplantation of cornea, when the endothelial cell is hurt, it becomes very difficult to maintain the transparency of the cornea. Therefore, it is very important not to hurt the endothelial cell to maintain the function of cornea after the operation. In general, at the above mentioned ophthalmic surgeries, an ophthalmic surgery auxiliary agent consisting of viscoelastic substance is used for the purpose to protect the cornea. The viscoelastic substance is poured into a camera anterior bulbi as to maintain the depth of camera anterior bulbi, and reduce the possibility of contact of tools to the endothelial cell of cornea and the surrounding tissue, further, the endothelial cell of cornea is protected from the mechanical harm by the adsorption of viscoelastic substances to the endothelial cell of cornea. Obviously, the most important physical feature required to the ophthalmic surgery auxiliary agent is that the material is a higher viscoelastic substance. Furthermore, since the auxiliary agent contacts to the operation part directly, not only the biological safety is required, but also the transparency is necessary not to hinder the view for the operation.
Usually, as the viscoelastic substance, solution of sodium hyaluronate or methyl cellulose are mainly used. Since these substances have a higher viscoelasticity, are superior at the biological safety and have an excellent transparency, they are suitable for the ophthalmic surgery auxiliary agent.
However, the high elasticity which is necessary as the ophthalmic surgery auxiliary agent causes a momentary rising of the intraocular pressure and accompanied with it a breakdown problem of barrier between blood and humor aqueous is caused after the operation, because the viscoelastic substance in camera anterior bulbi disturbs the discharge of aqueous humor which is circulating. Therefore, the procedure to remove the viscoelastic substance from camera anterior bulbi is carried out after the operation, however, because the viscoelasticity of it is too high, it is very difficult to remove it completely. And the problem of intraocular pressure rising certainly occurs after the operation. But the operation auxiliary agent is very useful for the operation and the intraocular pressure rising is only a momentary symptom, the operation auxiliary agent is still extensively used without any improvement.
Meanwhile, the utilization of collagen as the viscoelastic substance have been investigated for a long time. Collagen is a principal protein composing the body of animal, and has an excellent physical property as a biomaterial, which is recognized as a material having a good affinity to the cellular tissue of a living body and can be widely used for the medical device such as a trauma covering material, a hemostatic material and a restoration material for mollis tela recessus portio and so on. And the solution of it has not only a high viscoelasticity which is necessary as the ophthalmic surgery auxiliary agent, but also has a specific feature of collagen whose viscoelasticity can suddenly fall down by heating. That is, because of this special feature, the removal of the operation auxiliary agent after the operation becomes very easy.
However, the natural collagen or the solubilized collagen (aterocollagen) by an enzyme forms fibra in the neutral condition and the solution loses the transparency. Therefore, it is difficult to be used as the starting material of the ophthalmic surgery auxiliary agent which is necessary to have high viscosity and to be transparent. Further, the denaturing temperature of these kinds of collagen is higher than the intraocular temperature 35.degree. C., and since it takes a long time for the denaturation, it is necessary to be removed after the operation in the same manner to the other viscoelastic substance.
To avoid the above mentioned problem, an ophthalmic surgery auxiliary agent composed of a chemically modified collagen not to forming collagen fibra under the neutral condition is proposed. Namely, in the Japanese Patent publication 6-60200, a chemically modified collagen compound containing at least two natural collagen molecules, wherein at least one lysine .epsilon. amino group belonging to said collagen molecule is a chemically modified collagen compound bonded by a coupling group, said coupling group containing at least two parts selected from carbonyl and sulfonyl group, further said chemically modified collagen compound being soluble in a physiological buffer solution, is disclosed.
However, when said auxiliary agent is adopted for use in the eye which is a very sensitive organ, the safety of the coupling agent is a problem. Further, since by the intermolecular bonding, the lowering of viscoelasticity is controlled, it becomes necessary to be removed after the operation.
Further, in the Japanese patent application 53-49610, a succinylized collagen is disclosed as a chemically modified collagen which does not form fibra in neutral condition, and in the Japanese patent application 42-59201 a collagen solubilized by alkali is disclosed. These collagens do not form fibra and keep transparency in neutral condition, and since the denature temperature is lower than the intraocular temperature, viscoelasticity falls down quickly after the operation and is easy to be removed.
When an actual operation test is carried out on animal's eye using said disclosed substance as an auxiliary agent, the generation of white muddy substance is observed at the denaturing by the intraocular temperature. Accordingly, these substances are not desirable ones as the auxiliary agent. Namely, the maintenance of view for the operation is deteriorated, further, during the observation term after the operation, it becomes very difficult to distinguish the white muddy substance from an intraocular inflammation. Therefore, there is a possibility of a wrong diagnosis. Further, when the white muddy substance remains, it has a possibility of raising the intraocular pressure.